The objective of this work is the comparative study in vitro of the effect of two tumor suppressor genes, p53 and retinoblastoma (RB), on the multistep process of neoplastic transformation. Two culture systems will be used: (a) murine spleen-derived cells of the myelomonocyte/macrophage lineage, which require WEHI-3 cell conditioned medium (WEHI-CM) for their growth and (b) murine chondrocytes derived from the xiphisternum of adult mice, since they show a reproducible pattern of senescence. The following questions will be asked: 1. Does mutant p53 immortalize myeloid cells without the cells undergoing crisis (or senescence)? 2. Can v-myc induce growth factor independence in cells in which wildtype p53 activity is abrogated by mutant p53? 3. Does a high level of wildtype p53 expression lead to premature senescence and/or differentiation? 4. Does the murine RB gene also suppress early stages of neoplastic transformation, and does it cooperate with mutant p53 in suppressing the process of neoplastic progression? A better knowledge of the effect of tumor suppressor genes at different stages in the neoplastic transformation of myelomonocytes may lead to methods suppressing the growth of transformed myeloid cells before they develop into autonomously growing, fully tumorigenic blasts.